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Active transepithelial Cl − ‐secretion promotes hydrostatic lung edema
Author(s) -
Solymosi Esther Andrea,
Kaestle Stephanie M,
Vadász István,
Wang Liming,
Morty Rory,
Kuebler Wolfgang M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.696.10
Subject(s) - epithelial sodium channel , hydrostatic pressure , cystic fibrosis transmembrane conductance regulator , chemistry , secretion , bumetanide , reabsorption , edema , lung , amiloride , medicine , endocrinology , pulmonary edema , transepithelial potential difference , cystic fibrosis , cotransporter , kidney , ion transporter , sodium , biology , biochemistry , membrane , physics , organic chemistry , thermodynamics
Hydrostatic lung edema evolves from increased fluid filtration and inhibition of epithelial Na + channels (ENaC) that facilitate alveolar fluid clearance. Recently, we identified alveolar fluid secretion (AFS) as new key component in edema formation. Here, we tested whether Cl − secretion via cystic fibrosis transmemberane conductance regulator (CFTR) and Na + ‐K + ‐Cl − cotransporter 1 (NKCC1) may mediate AFS at elevated left atrial pressure (P LA ) and may be induced by inhibition of ENaC. In isolated lungs, we quantified AFS by a double indicator dilution technique, and transepithelial Cl − flux by radionuclide tracing and alveolar Cl − imaging. P LA elevation induced lung edema and AFS that coincided with transepithelial Cl − secretion and alveolar Cl − influx. These effects were blocked by inhibitors of CFTR, NKCC or Na + ‐K + ‐ATPase, and CFTR −/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride at physiological P LA induced AFS and Cl − secretion that were again CFTR‐, NKCC‐ and Na + ‐K + ‐ ATPase dependent. We conclude that transepithelial Cl − and fluid flux reverse from absorptive to secretory mode at hydrostatic stress as a result of ENaC inhibition, and are mediated by NKCC and CFTR.